Publications by authors named "Jeffrey J Pu"

Article Synopsis
  • - The study investigates the survival outcomes of patients receiving umbilical cord blood transplants (UCBT) across different racial and ethnic groups, focusing on Black, Latinx, White, and Asian patients, as previous research indicated disparities in survival rates.
  • - A retrospective analysis of data from the Center for International Blood and Marrow Transplant Research (CIBMTR) included 983 single and 1529 double UCBT recipients, measuring outcomes like overall survival (OS), disease-free survival, and transplant-related mortality over two years.
  • - Results showed that while overall survival rates varied by race/ethnicity, with Latinx patients having significantly lower OS compared to Blacks, no significant differences were observed in child patients,
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Aims: To investigate the mechanism of exosomes' role in the transformation of MDS to AML.

Methods: Exosomes in culture supernatants of MDS and AML cell lines, were extracted by ultrafiltration and identified in three ways: morphology, size, and exosome protein surface markers. Exosomes from AML cell lines were then co-cultured with MDS cell lines and their impacts on MDS cell microenvironment, proliferation, differentiation, cell cycle, and apoptosis were analyzed by CCK-8 assay and flow cytometry.

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Myelofibrosis (MF) is a disorder characterized by the proliferation of myeloid precursors, commonly due to overactive JAK signaling. The discovery of the JAK2 mutation and subsequent development of JAK inhibitors (JAKi) results in reduced spleen size, improved symptom, and enhanced survival in MF patients. However, there are unmet needs of additional novel targeted therapies for this incurable disease due to the limited utility of first-generation JAKis, which are associated with dose-limiting cytopenia and disease recurrence.

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Background: Umbilical cord blood hematopoietic stem cells are commonly used for hematopoietic system reconstitution in recipients after umbilical cord blood transplantation (UCBT). However, the optimal conditioning regimen for UCBT remains a topic of debate. The exact impact of total body irradiation (TBI) as a part of conditioning regimens remains unknown.

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Article Synopsis
  • Researchers created a prognostic model to predict outcomes for patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation by analyzing data from 623 patients in the U.S. (CIBMTR cohort) from 2000 to 2016.
  • They identified key factors that influence mortality, assigning weighted scores based on age, donor matching, hemoglobin levels, and donor compatibility, which resulted in differing survival rates among low, intermediate, and high score groupings.
  • The model was validated in a European cohort (EBMT), proving effective for predicting overall survival and transplant-related mortality, aiding clinicians in discussing transplantation prospects with myelofibrosis patients.
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Backgrounds: Chimeric antigen receptor (CAR)-T cell therapy has achieved unprecedented success in treating hematopoietic malignancies. However, this cell therapy is hampered in treating acute myeloid leukemia (AML) due to lack of ideal cell surface targets that only express on AML blasts and leukemia stem cells (LSCs) but not on normal hematopoietic stem cells (HSCs).

Methods: We detected the CD70 expression on the surfaces of AML cell lines, primary AML cells, HSC, and peripheral blood cells and generated a second-generation CD70-specific CAR-T cells using a construct containing a humanized 41D12-based scFv and a 41BB-CD3ζ intracellular signaling domain.

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Hodgkin lymphoma (HL) is a hematologic malignancy that comprises about 10% of all lymphomas with the most common type being classical HL (cHL). The typical clinical presentation of cHL involves multiple region lymphadenopathy and a chest mass found on imaging. However, not all patients present with the typical symptomology of cHL which poses a diagnostic challenge.

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Classical MCL (cMCL) constitutes 6-8% of all B cell NHL. Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes.

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Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone.

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The heterogeneity in disease pathology, the unpredictability in disease prognosis, and the variability in response to therapy make mantle cell lymphoma (MCL) a focus of novel therapeutic development. MCL is characterized by dysregulated expression of through a chromosome (11;14) translocation. MCL international prognostic index (MIPI), proliferation index, and mutation status are currently utilized for prognostication.

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Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) has been linked to the suppression of chromosomal instability. The spindle assembly checkpoint complex is responsible for proper chromosome segregation during mitosis to prevent chromosomal instability. In this study, the novel role of PIGN as a regulator of the spindle assembly checkpoint was unveiled in leukemic patient cells and cell lines.

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Antibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, "off-the-shelf" universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting.

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Immune thrombocytopenic purpura (ITP) is a hematological disorder characterized by immune-mediated destruction of platelets that could be triggered by a number of causes. ITPs are usually treated with steroid, immunomodulators or immunosuppressors, and intravenous immunoglobulin therapy though refractory/relapsed status frequently occurs. It was suggested that autologous hematopoietic stem cell transplant (HSCT) after high-dose chemotherapy conditioning might improve ITP patients' peripheral blood platelet counts via reorganizing disrupted immune balance in the hematopoietic and hematologic systems.

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Polyadenylation of pre-messenger RNA (pre-mRNA) specific sites and termination of their downstream transcriptions are signaled by unique sequence motif structures such as AAUAAA and its auxiliary elements. Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism that processes RNA products depending on its 3'-untranslated region (3'-UTR) specific sequence signal. APA processing can generate several mRNA isoforms from a single gene, which may have different biological functions on their target gene.

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Article Synopsis
  • Intolerance to previous kinase inhibitors is a major reason for discontinuation in patients with chronic lymphocytic leukemia (CLL), prompting the trial of umbralisib, a new and selective PI3Kδ/CK1ε inhibitor.
  • A phase 2 trial involving 51 previously treated CLL patients, who were intolerant to other treatments, showed that umbralisib had a median progression-free survival (PFS) of 23.5 months while maintaining a better tolerance than earlier therapies.
  • The study indicated that a significant portion of patients (58%) remained on umbralisib longer than their initial treatments despite some experiencing adverse events, confirming umbralisib's potential as a viable option for this intoler
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  • Limited information exists on the effectiveness of bendamustine and rituximab (BR) in treating chronic lymphocytic leukemia (CLL) in patients with renal issues or other health conditions, leading to a study comparing this treatment to ibrutinib in real-world scenarios.
  • A study involved 157 patients with lower kidney function or multiple health problems, finding that while BR was effective, those with TP53 gene disruption had shorter progression-free survival (PFS) and increased risk of death.
  • The analysis revealed that ibrutinib had better PFS outcomes for advanced-stage patients compared to BR, suggesting that while BR works for some, ibrutinib may offer better long-term control for more severe cases.
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  • Venetoclax-based therapy is a standard treatment for chronic lymphocytic leukemia (CLL), but how to manage patients after stopping it is unclear.
  • A study involving 326 patients who discontinued venetoclax explored their responses to different treatments, focusing on overall response rate and progression-free survival.
  • Results indicated that BTK inhibitors were highly effective for patients who had not previously received them, while less effective for those who had, and PI3K inhibitors provided limited benefit, highlighting the importance of treatment history when selecting post-venetoclax therapies.
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Hydroxyurea (HU) has been widely used in sickle cell disease. Its potential long-term risk for carcinogenesis or leukemogenic risk remains undefined. Here, we report a 26 y old African-American female with Sickle Cell Disease (SCD) who developed refractory/relapsed acute myeloid leukemia (AML) 6 months after 26 months of HU use.

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Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology.

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Article Synopsis
  • - A study found that Ibrutinib offers better response rates and survival for chronic lymphocytic leukemia (CLL) patients not included in earlier trials, particularly those under 65 and with a specific chromosome deletion (del[17p13]).
  • - Out of 391 CLL patients examined, 57% were excluded from previous pivotal studies, with 41% being under 65 and 30% having del(17p13), showing that those under 65 were more likely to start on a higher dose of Ibrutinib, impacting their progression-free survival (PFS).
  • - Common side effects included fatigue and rash, with 24% of patients stopping the treatment within about 14 months, often
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Article Synopsis
  • Venetoclax is a BCL2 inhibitor used to treat chronic lymphocytic leukemia (CLL) patients with specific genetic mutations, showing effectiveness even after previous kinase inhibitor treatments.
  • A study of 141 CLL patients revealed a 72% overall response rate to Venetoclax, with common side effects including neutropenia and thrombocytopenia, but many patients reached the maximum recommended dosage.
  • Further research is needed to determine the best order for using newer CLL therapies, as many patients successfully transitioned to other treatments like ibrutinib after stopping Venetoclax.
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